thromboxane-b2 and Swine-Diseases

The clinical and anti-inflammatory effects of a single treatment of 0.4 mg meloxicam/kg bodyweight on pigs that had been challenged with Escherichia coli endotoxin were investigated. Significantly lower total clinical scores were recorded in pigs treated with meloxicam than in pigs treated with a placebo. Significantly higher mean serum concentrations of thromboxane B(2) were also recorded in pigs treated with a placebo for up to 24 hours after the challenge. The serum concentrations of acute phase proteins and specific antibody titres to E coli lipopolysaccharide were unaffected by the meloxicam. The meloxicam treatment was well tolerated.

Topics: Acute-Phase Proteins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Bacterial; Endotoxemia; Escherichia coli; Escherichia coli Infections; Female; Immunoglobulin G; Lipopolysaccharides; Male; Meloxicam; Single-Blind Method; Swine; Swine Diseases; Thiazines; Thiazoles; Thromboxane B2; Treatment Outcome

Non-steroidal anti-inflammatory drugs (NSAID) are a family of chemicals that function to reduce pain, fever, and inflammation, and they are commonly used in people and animals for this purpose. Currently there are no NSAIDs approved for the management of inflammation in swine due to a lack of validated animal models and suitable biomarkers to assess efficacy. A previous in vitro study examining biomarkers of inflammation identified fourteen genes that were significantly altered in response to Escherichia coli lipopolysaccharide (LPS)-induced inflammation. In the present study, five of those fourteen genes were tested in vivo to determine if the same effects observed in vitro were also observed in vivo. Plasma levels of prostaglandin E(2) (PGE(2)), an essential mediator of fever and inflammation, were also determined. Two groups of swine were stimulated with LPS with the second group also treated with flunixin meglumine. Blood was collected at 0, 1, 3, 6, 8, 24, and 48 h post LPS-stimulation. The RNA was extracted from the blood and quantitative real-time-PCR (qRT-PCR) was utilized to determine the expression patterns of CD1, CD4, serum amyloid A2 (SAA2), Caspase 1, and monocyte chemoattractant protein 1 (MCP-1). The LPS-stimulated animals demonstrated a statistically significant alteration in expression of SAA2 and CD1 at 3h post-stimulation. Flunixin meglumine treated animals' demonstrated reduced expression of CD1 in comparison to the LPS-stimulated swine at 24 and 48 h post LPS-stimulation. Flunixin meglumine treated animals exhibited reduced expression of SAA2 at 48 h post-stimulation compared to LPS-stimulated swine. Swine treated with LPS demonstrated statistically significant increases in plasma PGE(2) at 1h post-stimulation. Swine treated with flunixin meglumine had no increase in plasma PGE(2) levels at any time. These results demonstrate that PGE(2) production, along with two out of five genes (SAA2 and CD1) have the potential to serve as early biomarkers of inflammation as well as indicators of NSAID efficacy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, CD1; Biomarkers; Caspase 1; CD4 Antigens; Chemokine CCL2; Clonixin; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Inflammation; Lipopolysaccharides; Male; Real-Time Polymerase Chain Reaction; Serum Amyloid A Protein; Swine; Swine Diseases; Thromboxane B2

In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B(2) and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B(2) concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Endotoxins; Female; Ketoprofen; Male; Pain; Pain Measurement; Random Allocation; Swine; Swine Diseases; Thromboxane B2

The interaction between constitutive nitric oxide and oxygen may depend on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia. We investigated if hyperoxia (100% O2) attenuated the systemic and pulmonary vasoconstriction and increased biosynthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin (PG) F1alpha induced by inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15.4 +/- 2.7 kg (mean +/- standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O2, orotracheally intubated and ventilated to maintain normocapnia, and then instrumented for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O2 (Control, n = 6); Escherichia coli lipopolysaccharide (5 microg/kg/h from 1 to 2 h followed by 2 microg/kg/h from 2 to 5 h) + 30% O2 (LPS, n = 4); L-NAME (0.5 mg/kg/h, from 0 to 5 h) + LPS + 100% O2 (n = 6); and L-NAME + LPS + 30% O2 (n = 6). L-NAME and endotoxin significantly (P < 0.05) increased mean arterial pressure, mean pulmonary arterial pressure, and systemic and pulmonary vascular resistance index beginning at 90 min. When results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O2 group than all other groups, reflecting pulmonary and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LPS-induced increases in TXB2 and 6-keto-PGF1alpha concentrations at 90 and 120 min and 120 min, respectively, although the differences were not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious haemodynamic effects in this model of endotoxaemia. The temporal attenuation of L-NAME-induced pulmonary and systemic vasoconstriction by hyperoxia suggested that the haemodynamic effects of acute endotoxaemia were in part influenced by the relative amounts of nitric oxide and oxygen present.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Endotoxemia; Enzyme Inhibitors; Escherichia coli Infections; Hemodynamics; Hyperoxia; Lung; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pulmonary Circulation; Swine; Swine Diseases; Thromboxane B2; Vasoconstriction

An autosomal recessive thrombopathy in pigs is described and characterized functionally, morphologically and biochemically. The affected pigs have a severe bleeding diathesis and a markedly prolonged bleeding time but normal plasma and platelet von Willebrand factor (vWF) levels. Electron micrographs and fluorescence microscopy with mepacrine reveal reduced numbers of dense granules in platelets as compared to normals. This thrombopathy is a pure delta storage pool disease (SPD), as evidenced: a) biochemically by platelet serotonin content and metabolism and by comparative ATP/ADP content and secretion; b) functionally by reduced aggregability to low concentrations of convulxin and collagen but normal aggregability to other agents and normal synthesis of thromboxane B2. The affection was first discovered in a colony of von Willebrand's disease (vWD) pigs, but is biologically and genetically distinct. It is possible to completely separate the SPD from the vWD, although originally animals could be affected by both vWD and SPD. Normal plasma and platelet alpha granule content of vWF are found in diseased animals. An intermediate disorder is also detected in animals not severely affected, which may represent the heterozygous state.

Topics: Acetylserotonin O-Methyltransferase; Adenine Nucleotides; Animals; Arylamine N-Acetyltransferase; Blood Platelets; Cytoplasmic Granules; Genes, Recessive; Microscopy, Electron; Platelet Aggregation; Platelet Storage Pool Deficiency; Serotonin; Swine; Swine Diseases; Thromboxane B2; von Willebrand Diseases; von Willebrand Factor

The stable metabolites of thromboxane A2, prostaglandin E2, and prostaglandin F2 alpha (TxB2, PgEM, and PgFM, respectively) were measured in the blood plasma of nine castrated male pigs, each inoculated with 2 x 10(5) sporocysts of Sarcocystis miescheriana (group A), and in that of nine non-infected controls (group B). All infected pigs developed mild disease, the clinical signs being most severe between days 14 and 17 post infection (p.i.). In the infected pigs of group A, the TxB2 plasma levels increased with the onset of the acute phase of illness (12 days p.i.), reaching peak values at day 14 p.i. The mean TxB2 values were significantly higher in the infected pigs from day 12 p.i. until the termination of the experiment on day 21 p.i. The PgEM values increased steadily in the infected pigs from day 12 p.i. until day 21 p.i. but remained relatively constant in the control pigs during the same period. In contrast, PgFM values remained low in the infected pigs throughout the experiment, and no significant differences between infected and non-infected pigs could be found. We conclude that the elevated TxB2 and PgEM values reflect a major involvement of prostanoids in the pathogenesis of sarcocystiosis.

Topics: Animals; Dinoprost; Dinoprostone; Male; Sarcocystosis; Swine; Swine Diseases; Thromboxane B2

Changes in the production of proaggregatory (thromboxane A2 and prostaglandin E2) and antiaggregatory (prostacyclin) prostaglandins by blood platelets, macrophages and endothelial cells during acute African swine fever caused by both a highly virulent virus and a less virulent virus were studied. No impairment in thromboxane A2 release by either platelets or macrophages could be detected but prostacyclin production by the endothelium was impaired. There was also a significant increase in prostaglandin E2 release by macrophages at the time when thrombocytopenia was most marked. However, the early event that causes primary aggregation remains obscure.

Topics: African Swine Fever; Animals; Arachidonic Acids; Blood Coagulation; Blood Platelets; Dinoprostone; Endothelium; Hematocrit; Hemorrhage; Macrophages; Platelet Aggregation; Platelet Function Tests; Prostaglandins E; Swine; Swine Diseases; Thrombocytopenia; Thromboxane B2